effects or for better control of confounding, it can also be highly efficient for studying interaction effects. For example, Li et al.47 used a two-phase design nested within the Atherosclerosis Risk in Communities (ARIC) study to study the interaction between GSTM1/GSTT1 and cigarette smoking on the risk of coronary heart disease. Their sampling scheme was not fully efficient for addressing this particular question because it stratified only on intima media thickness, not smoking, and only for the controls, and did not exploit the information from the original cohort in the analysis. Reanalyses of other data from the ARIC study48 showed the considerable improvement in efficiency that can be obtained by using the full cohort information.
